Functionalizing metal nanoclusters in water: Synthesis, interfacing, and emerging applications

Atomically precise metal nanoclusters (MNCs) are metallic kernels wrapped by ligand shells whose chemistry dictates solubility, stability, and interfacial reactivity. Focusing on water-soluble MNCs, this review treats the interface as the bridge from synthesis to function. We map out both direct aqueous syntheses and gentle postsynthetic routes that install hydrophilic motifs while preserving atomic structures. Design rules are then codified: interfacial structure controls stability and mobility, recognition at the interface dictates selectivity, and the local environment sets charge transfer and photophysical responses. Furthermore, ligand shells can define nanoscopic reaction pockets that steer substrate approach and govern electron or energy transfer. These principles illuminate unique advantages in bioimaging and labeling, enzyme-compatible sensing, and controlled charge and mass transport for electrocatalysis. By consolidating synthesis, interfacial physics, and use cases within one framework, this review provides actionable guidelines for linking molecular structure to macroscopic performance and for rationally engineering aqueous MNCs for biomedical and catalytic applications.